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Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis

Genes & Immunity volume 13, pages 573–578 (2012)Cite this article

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Abstract

Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms. Genome-wide association studies in European populations have reported significant associations between sarcoidosis and single-nucleotide polymorphisms (SNPs) located in the intergenic region between the C10ORF67 and OTUD1 genes on chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine-mapping at 10p12 and 10q22 to assess associations of genetic variants in these regions with sarcoidosis risk in African-American women, based on 486 sarcoidosis cases and 943 age- and geography-matched controls in a nested case–control study within the Black Women’s Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67–OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). Both SNPs are located inside an ∼300 kb low recombination region of chromosome 10p12, suggesting that both SNPs are tagging the same causal variant. Our top SNP (rs11013452) is located inside a smaller linkage disequilibrium block in HapMap YRI, further narrowing the position of the causal SNP to a region of ∼8 kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis.

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Acknowledgements

This work was supported by Grant K01HL088709 from the National Heart, Lung, and Blood Institute and Grant CA058420 from the Division of Cancer Control and Population Science, National Cancer Institute (http://www.cancercontrol.cancer.gov). CJ McKinnon was supported by the Graduate Research Assistant Scholarship Program (GRASP) of the Boston University Graduate School of Arts and Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

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Authors and Affiliations

  1. Slone Epidemiology Center at Boston University, Boston, MA, USA

    Y C Cozier, E A Ruiz-Narvaez, C J McKinnon, L Rosenberg & J R Palmer

  2. Department of Mathematics and Statistics, Boston University Graduate School of Arts and Sciences, Boston, MA, USA

    C J McKinnon

  3. The Pulmonary Center at Boston University, School of Medicine, Boston, MA, USA

    J S Berman

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  1. Y C Cozier
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Correspondence to Y C Cozier.

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Cozier, Y., Ruiz-Narvaez, E., McKinnon, C. et al. Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis. Genes Immun 13, 573–578 (2012). https://doi.org/10.1038/gene.2012.42

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